**Background:** Epilepsy is a common neurological disorder affecting 70 million people worldwide, with a global lifetime prevalence of 7.6 per 1000 persons and a peak incidence in patients aged 20–29 years. In the pediatric age group, epilepsy affects approximately 0.5–1% of children. Comorbidities are present in nearly 50% of people with epilepsy, and the risk of comorbidities may reach eight times higher than in the general population. Attention deficit hyperactivity disorder (ADHD) is one of the most common psychiatric comorbidities in children with epilepsy (CWE), characterized by impaired attention, impulsivity, and hyperactivity. Despite the high burden, comorbid ADHD remains under-recognized in clinical practice. This narrative review aims to summarize the burden, mechanisms of association, and management challenges of ADHD in childhood epilepsy.
**Methods:** This is a narrative review synthesizing published literature on the epidemiology, mechanisms, diagnosis, and management of ADHD in CWE. The authors adopted the framework proposed by Keezer et al. (2016) to classify potential mechanisms of association into five categories: chance, causative mechanisms, resultant mechanisms, shared genetics, and shared risk factors. The review also examines evidence from clinical trials, observational studies, and registry data regarding stimulant safety and efficacy in this population.
**Key Results:** The reported prevalence of ADHD in CWE ranges from 12–77%, compared to 3–5% in the general pediatric population. Large population-based studies show CWE have a 2-to-7-fold higher risk of ADHD than the general population. The primarily inattentive presentation is more common in CWE than other presentations. A population-based study from Taiwan demonstrated a 2.54-fold increased risk of subsequent ADHD in CWE compared to controls, while children with new-onset ADHD had a 3.94-fold increased risk of subsequent epilepsy, establishing a bidirectional connection. Genetic correlation explains approximately 40% of the phenotypic correlation between epilepsy and ADHD. Regarding treatment, two double-blind trials showed methylphenidate (MPH) achieved a response rate of 60–70% in CWE with comorbid ADHD. In controlled trials involving patients with refractory epilepsy, MPH had a response rate of 63–73%. A retrospective study of 18,166 stimulant users and 54,197 non-users in CWE found no difference in the risk of seizure-related hospitalization between users and non-users. A population-based study of 29,604 ADHD children on MPH from Hong Kong reported an incidence of new-onset seizures of only 0.2% (4.4 per 10,000 patient-years), though seizure risk increased during the first month after treatment but not after three months. Several studies consistently showed no increase in seizure risk with stimulants, including in patients with poorly controlled epilepsy.
**Clinical Implications:** The well-established bidirectional connection and shared genetic/non-genetic factors between epilepsy and ADHD largely rule out the possibility of a chance association. Early identification and management of comorbid ADHD are crucial to optimize prognosis and reduce the risk of adverse long-term neurodevelopmental outcomes. Stimulants, particularly methylphenidate, are effective and safe in CWE within approved doses, though safety data should be further studied in randomized, double-blinded, placebo-controlled trials. The ILAE 2017 classification emphasizes identifying comorbidities as integral components during epilepsy evaluation. The identification of shared genetic backgrounds—including chromosomal abnormalities such as 5q14.3 and 7p22.3, and SNPs involving MEF2C and MECP2—may open the gate for precision medicine approaches. Clinicians should consider choosing ASMs with favorable cognitive profiles (e.g., lamotrigine, carbamazepine, oxcarbazepine) and be aware that valproate and polypharmacy may worsen inattentive symptoms. Non-pharmacological approaches, particularly behavior therapy with parent training, show statistically significant results and may be especially relevant when there are medical contraindications or parental preference to minimize medications.